Identification of dihydropyrimidinase-related protein 4 as a novel target of the p53 tumor suppressor in the apoptotic response to DNA damage.

Abstract

The p53 tumor suppressor gene, which is frequently mutated in a wide variety of tumors, plays an important role in maintaining genomic integrity. Following genotoxic insults, the protein level of p53 is increased, and p53 functions as a sequence-specific transcription factor that regulates the expression of downstream target genes required for cell cycle arrest, DNA repair or apoptosis. However, the mechanism for p53-inducible apoptosis remains largely unclear. To search novel downstream targets of p53 on apoptosis, we had carried out microarray analysis. We identified dihydropyrimidinase-related protein (DPYSL) 4 gene, which was upregulated by overexpressing p53 in p53-deficient cells. Both mRNA and protein expressions of DPYSL4 were specifically induced by anticancer agents in p53-proficient cells. Further analyses demonstrated that DPYSL4 was a direct target for p53. We also found that genotoxic-induced apoptosis was repressed in cells silenced for DPYSL4. These findings indicate that DPYSL4 is a novel apoptosis-inducible factor controlled by p53 in response to DNA damage.

• Authors: Junko Kimura, Takuya Kudoh, Yoshio Miki, Kiyotsugu Yoshida
• Journal: International journal of cancer (Int J Cancer) Vol. 128 Issue 7 Pg. 1524-31 (Apr 01 2011) ISSN: 1097-0215 [Electronic] United States
• PMID: 20499313 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 UICC.

Chemical References

• DPYSL4 protein, human
• Dpysl4 protein, mouse
• Nerve Tissue Proteins
• TP53 protein, human
• Tumor Suppressor Protein p53
• Ubiquitin

Topics

• Animals
• Apoptosis
• Cell Cycle
• Cell Line, Tumor
• DNA Damage
• Genes, p53
• Humans
• Mice
• Nerve Tissue Proteins (metabolism)
• Oligonucleotide Array Sequence Analysis
• Transcription, Genetic
• Tumor Suppressor Protein p53 (metabolism)
• Ubiquitin (chemistry)